Carvacrol, thymol, gallic acid를 함유한 필름 개발과 그 특성 규명 : 소고기 패티 저장 시의 적용

학위논문 (석사) -- 서울대학교 대학원 : 농업생명과학대학 식품공학과, 2021. 2. 강동현.Recently, active packaging is regarded as a promising approach to extend the shelf-life of food. In this regard, novel active films, chitosan-starch films containing carvacrol, thymol and gallic acid, were developed and characterized. Our results exhibited that incorporation of gallic acid in chitosan-starch films increased color changes, tensile strength, antioxidant activity and decreased elongation at break, water vapor permeability of the films. The films with carvacrol and thymol showed an increase in ductility, color changes, antioxidant activity, antimicrobial effect and decreasing tensile strength, water vapor permeability. Furthermore, by the addition of both gallic acid and essential oils, films presented the best mechanical, water barrier properties and the strongest antioxidant and antimicrobial activity. Finally, the application of the blending film to the preservation of beef patties was performed. The results showed that the films containing carvacrol and gallic acid effectively prevented lipid peroxidation and reduced total viable cell population of ground beef patties. This study showed the benefits of the incorporation of gallic acid, carvacrol and thymol into chitosan-starch films and the potential of their use as active packaging in food products.최근 활성 포장이 식품의 유통기한을 연장할 수 있는 유망한 방법으로 간주 됨에 따라 새로운 활성 포장 필름의 개발이 중요해지고 있다. 이에 따라 새로운 활성 필름인 카바크롤, 티몰, 갈산을 첨가한 키토산-전분 필름을 개발했고 그 특성을 규명하였다. 실험 결과를 통해 키토산-전분 필름에 갈산을 첨가했을 때, 갈산이 폴리머와 결합할 수 있는 성질에 의해 필름의 인장 강도가 증가하고 연신율과 수증기 투과도는 감소하는 것을 확인했다. 카바크롤과 티몰을 키토산-전분 필름에 첨가했을 경우 연신율, 색 변화, 항산화, 항균 효과는 증가하고 인장 강도, 수증기 투과도는 감소하는 경향을 보였다. 더 나아가, 필름에 갈산과 에센셜 오일을 같이 넣었을 때 필름은 가장 뛰어난 기계적 성질과 수증기 장벽으로서의 성질을 보일 뿐만 아니라 가장 강력한 항산화, 항균 효과를 보였다. 마지막으로, 필름을 소고기 패티 보관에 적용하여 그 효과를 확인했다. 결과를 통해 갈산과 카바크롤을 같이 첨가한 필름은 소고기 패티 저장 시 높은 항산화, 항균 효과를 보이는 것을 확인하였다. 이 연구를 통해 키토산-전분 필름에 갈산, 카바크롤, 티몰을 첨가함으로써 얻는 다양한 이점을 알 수 있었고, 실제 식품에 적용할 수 있는 가능성을 확인하였다.I. INTRODUCTION 11 II. MATERIALS AND METHODS 15 2.1. Materials 15 2.2. Film preparation 15 2.3. Film properties 18 2.3.1. Optical properties 18 2.3.1.1. Color 18 2.3.1.2. Transparency 18 2.3.2. Film thickness 19 2.3.3. Mechanical properties 19 2.3.4. Physical properties 20 2.3.4.1. Moisture content 20 2.3.4.2. Water vapor permeability 20 2.3.5. Scanning electron microscopy 21 2.3.6. Antioxidant activity 21 2.3.7. Antimicrobial activity 22 2.3.7.1. Inoculum preparation 22 2.3.7.2. Disk diffusion assay 22 2.3.7.3. Food solid system 22 2.4. Application to beef patties storage 23 2.4.1. Preparation of beef patties 23 2.4.2. Thiobarbituric acid reactive substances 24 2.4.3. Color 24 2.4.4. Total viable cell count 24 2.5. Statistical analysis 25 III. RESULTS AND DISCUSSION 26 3.1. Film properties 26 3.1.1. Optical characteristic 26 3.1.2. Mechanical properties 31 3.1.3. Thickness, water vapor permeability, moisture contents 33 3.1.4. SEM 36 3.1.5. Antioxidant activity 40 3.1.6. Antimicrobial effect 42 3.2. Application to beef patties storage 46 3.2.1. Thiobarbituric acid reactive substances 46 3.2.2. Color 48 3.2.3. Total viable cell count 51 IV. CONCLUSION 53 V. REFERENCES 54 VI. 국문초록 58Maste

High endothelial venule is a surrogate biomarker for T-cell inflamed tumor microenvironment and prognosis in gastric cancer

Background: High endothelial venule (HEV) is a specialized vasculature for lymphocyte trafficking. While HEVs are frequently observed within gastric cancer (GC), the vascular-immune interaction between HEV and tumor-infiltrating lymphocytes (TILs) has not been well elucidated. In this study, we aimed to unveil the potential value of HEVs as a surrogate marker for T-cell inflamed immune microenvironment in GC using a large number of prospectively collected surgical specimens of GC. Methods: We included 460 patients with GC who underwent surgical resection. Nanostring PanCancer immune profiling was performed to evaluate the immunological phenotype of GCs. HEV density and three distinct patterns of TILs (Crohn-like lymphoid reaction, peritumoral lymphoid reaction, and intratumoral lymphoid reaction) were analyzed for their relationship and evaluated as prognostic factors for relapse-free survival (RFS) and overall survival (OS). Results: HEV-high GC revealed increased infiltration by immune cell subsets, including dendritic cells, CD8+ cytotoxic T cells, and CD4+ helper T cells. In addition, HEV-high GC demonstrated increased immune-modulating chemokines, type I or II interferon pathway, and immune checkpoints, all of which indicate the inflamed tumor microenvironment (TME). All three distinct patterns of TILs were associated with HEV density. In survival analysis, patients with HEV-high GC displayed significantly longer RFS and OS than those with HEV-low GC (p<0.001 for RFS, p<0.001 for OS). Multivariate analysis demonstrated that HEV was the most significant immunological prognostic factor for RFS (patients with high HEV compared with those with low HEV; HR 0.412, 95% CI 0.241 to 0.705, p=0.001) and OS (HR 0.547, 95% CI 0.329 to 0.909, p=0.02) after adjustment for age, stage, and TIL. Conclusion: HEV is the most significant immunological prognosticator for RFS and OS in resected GC, indicating inflamed TME.ope

Patient-specific virtual three-dimensional surgical navigation for gastric cancer surgery: A prospective study for preoperative planning and intraoperative guidance

Introduction: Abdominal computed tomography (CT) can accurately demonstrate organs and vascular structures around the stomach, and its potential role for image guidance is becoming increasingly established. However, solely using two-dimensional CT images to identify critical anatomical structures is undeniably challenging and not surgeon-friendly. To validate the feasibility of a patient-specific 3-D surgical navigation system for preoperative planning and intraoperative guidance during robotic gastric cancer surgery. Materials and methods: A prospective single-arm open-label observational study was conducted. Thirty participants underwent robotic distal gastrectomy for gastric cancer using a virtual surgical navigation system that provides patient-specific 3-D anatomical information with a pneumoperitoneum model using preoperative CT-angiography. Turnaround time and the accuracy of detecting vascular anatomy with its variations were measured, and perioperative outcomes were compared with a control group after propensity-score matching during the same study period. Results: Among 36 registered patients, 6 were excluded from the study. Patient-specific 3-D anatomy reconstruction was successfully implemented without any problems in all 30 patients using preoperative CT. All vessels encountered during gastric cancer surgery were successfully reconstructed, and all vascular origins and variations were identical to operative findings. The operative data and short-term outcomes between the experimental and control group were comparable. The experimental group showed shorter anesthesia time (218.6 min vs. 230.3 min; P=0.299), operative time (177.1 min vs. 193.9 min; P=0.137), and console time (129.3 min vs. 147.4 min; P=0.101) than the control group, although the differences were not statistically significant. Conclusions: Patient-specific 3-D surgical navigation system for robotic gastrectomy for gastric cancer is clinically feasible and applicable with an acceptable turnaround time. This system enables patient-specific preoperative planning and intraoperative navigation by visualizing all the anatomy required for gastrectomy in 3-D models without any error. Clinical trial registration: Clinicaltrials.gov, identifier NCT05039333.ope

Securing Resection Margin Using Indocyanine Green Diffusion Range on Gastric Wall during NIR Fluorescence-Guided Surgery in Early Gastric Cancer Patients

Near-infrared (NIR) fluorescence lymphography-guided minimally invasive gastrectomy using indocyanine green (ICG) is employed to visualize draining lymphatic vessels and lymph nodes. Endoscopically injected ICG spreads along the gastric wall and emits fluorescence from the serosal surface of the stomach. We aimed to assess the efficacy of ICG diffusion in securing the resection margin. We retrospectively analyzed 503 patients with early gastric cancer located in the body of the stomach who underwent fluorescence lymphography-guided gastrectomy from 2018 to 2021. One day before surgery, ICG was endoscopically injected into four points of the submucosal layer peritumorally. We measured the extent of resection and the resection line based on the ICG diffusion area from the specimen using NIR imaging. The mean area of the ICG diffusion was 82.7 × 75.3 and 86.7 × 80.2 mm2 on the mucosal and serosal sides, respectively. After subtotal gastrectomy, the length of the proximal resection margin was 38.1 ± 20.1, 33.4 ± 22.2, and 28.7 ± 17.2 mm in gastroduodenostomy, loop gastrojejunostomy, and Roux-en-Y gastrojejunostomy, respectively. The ICG diffusion area along the gastric wall secured a resection margin of &gt;28 mm. The ICG diffusion range can be used as a simple and easy method for determining the resection margin during gastrectomy using NIR imaging.ope

Robotic versus Laparoscopic versus Open Gastrectomy: A Meta-Analysis.

PURPOSE: To define the role of robotic gastrectomy for the treatment of gastric cancer, the present systematic review with meta-analysis was performed. MATERIALS AND METHODS: A comprehensive search up to July 2012 was conducted on PubMed, EMBASE, and the Cochrane Library. All eligible studies comparing robotic gastrectomy versus laparoscopic gastrectomy or open gastrectomy were included. RESULTS: Included in our meta-analysis were seven studies of 1,967 patients that compared robotic (n=404) with open (n=718) or laparoscopic (n=845) gastrectomy. In the complete analysis, a shorter hospital stay was noted with robotic gastrectomy than with open gastrectomy (weighted mean difference: -2.92, 95% confidence interval: -4.94 to -0.89, P=0.005). Additionally, there was a significant reduction in intraoperative blood loss with robotic gastrectomy compared with laparoscopic gastrectomy (weighted mean difference: -35.53, 95% confidence interval: -66.98 to -4.09, P=0.03). These advantages were at the price of a significantly prolonged operative time for both robotic gastrectomy versus laparoscopic gastrectomy (weighted mean difference: 63.70, 95% confidence interval: 44.22 to 83.17, P<0.00001) and robotic gastrectomy versus open gastrectomy (weighted mean difference: 95.83, 95% confidence interval: 54.48 to 137.18, P<0.00001). Analysis of the number of lymph nodes retrieved and overall complication rates revealed that these outcomes did not differ significantly between the groups. CONCLUSIONS: Robotic gastrectomy for gastric cancer reduces intraoperative blood loss and the postoperative hospital length of stay compared with laparoscopic gastrectomy and open gastrectomy at a cost of a longer operating time. Robotic gastrectomy also provides an oncologically adequate lymphadenectomy. Additional high-quality prospective studies are recommended to better evaluate both short and long-term outcomes.ope

Safe Discharge Criteria After Curative Gastrectomy for Gastric Cancer

Purpose: This study aimed to investigate the relationship between clinical and laboratory parameters and complication status to predict which patients can be safely discharged from the hospital on the third postoperative day (POD). Materials and methods: Data from a prospectively maintained database of 2,110 consecutive patients with gastric adenocarcinoma who underwent curative surgery were reviewed. The third POD vital signs, laboratory data, and details of the course after surgery were collected. Patients with grade II or higher complications after the third POD were considered unsuitable for early discharge. The performance metrics were calculated for all algorithm parameters. The proposed algorithm was tested using a validation dataset of consecutive patients from the same center. Results: Of 1,438 patients in the study cohort, 142 (9.9%) were considered unsuitable for early discharge. C-reactive protein level, body temperature, pulse rate, and neutrophil count had good performance metrics and were determined to be independent prognostic factors. An algorithm consisting of these 4 parameters had a negative predictive value (NPV) of 95.9% (95% confidence interval [CI], 94.2-97.3), sensitivity of 80.3% (95% CI, 72.8-86.5), and specificity of 51.1% (95% CI, 48.3-53.8). Only 28 (1.9%) patients in the study cohort were classified as false negatives. In the validation dataset, the NPV was 93.7%, sensitivity was 66%, and 3.3% (17/512) of patients were classified as false negatives. Conclusions: Simple clinical and laboratory parameters obtained on the third POD can be used when making decisions regarding the safe early discharge of patients who underwent gastrectomy.ope

Korean Practice Guidelines for Gastric Cancer 2022: An Evidence-based, Multidisciplinary Approach

Gastric cancer is one of the most common cancers in Korea and the world. Since 2004, this is the 4th gastric cancer guideline published in Korea which is the revised version of previous evidence-based approach in 2018. Current guideline is a collaborative work of the interdisciplinary working group including experts in the field of gastric surgery, gastroenterology, endoscopy, medical oncology, abdominal radiology, pathology, nuclear medicine, radiation oncology and guideline development methodology. Total of 33 key questions were updated or proposed after a collaborative review by the working group and 40 statements were developed according to the systematic review using the MEDLINE, Embase, Cochrane Library and KoreaMed database. The level of evidence and the grading of recommendations were categorized according to the Grading of Recommendations, Assessment, Development and Evaluation proposition. Evidence level, benefit, harm, and clinical applicability was considered as the significant factors for recommendation. The working group reviewed recommendations and discussed for consensus. In the earlier part, general consideration discusses screening, diagnosis and staging of endoscopy, pathology, radiology, and nuclear medicine. Flowchart is depicted with statements which is supported by meta-analysis and references. Since clinical trial and systematic review was not suitable for postoperative oncologic and nutritional follow-up, working group agreed to conduct a nationwide survey investigating the clinical practice of all tertiary or general hospitals in Korea. The purpose of this survey was to provide baseline information on follow up. Herein we present a multidisciplinary-evidence based gastric cancer guideline.ope

Fluorescent Lymphography-Guided Lymphadenectomy during Minimally Invasive Completion Total Gastrectomy for Remnant Gastric Cancer Patients

No study has evaluated fluorescent lymphography for lymphadenectomy in remnant gastric cancer (RGC). This study aimed to assess the clinical application of fluorescent lymphography in minimally invasive completion total gastrectomy for RGC. Patients who had undergone minimally invasive completion total gastrectomy for RGC from 2013 to 2020 were retrospectively reviewed. The perioperative outcomes and long-term prognosis were compared between patients who had undergone minimally invasive completion total gastrectomy with fluorescent lymphography (the FL group) and those without fluorescent lymphography (the non-FL group). The FL group comprised 32 patients, and the non-FL group comprised 36 patients. FL visualized lymphatics in all 32 patients without complications related to the fluorescent injection. The median number [the interquartile range] of LN retrieval was significantly higher in the FL group (17 [9.3-23.5]) than in the non-FL group (12.5 [4-17.8]); p = 0.016). The sensitivity of fluorescent lymphography in detecting metastatic LN stations was 75%, and the negative predictive value was 96.9% in the FL group. The overall relapse-free survivals were comparable between the groups (p = 0.833 and p = 0.524, respectively). FL is an effective tool to perform a more thorough lymphadenectomy during minimally invasive completion total gastrectomy for RGC. Using FL in RGC surgery may improve surgical quality and proper staging.ope

Prognostic Value of Postoperative Neutrophil and Albumin: Reassessment One Month After Gastric Cancer Surgery

Objective: The prognostic value of postoperative parameters reflecting the inflammatory and nutritional status of patients undergoing cancer surgery has been rarely studied. This study investigated the prognostic value of inflammatory and nutritional parameters measured preoperatively and 1 month after curative gastrectomy for gastric cancer. Methods: Data from a prospectively maintained database of 1,194 patients with gastric cancer who underwent curative surgery in 2009-2018 were retrospectively reviewed. Demographics, clinicopathologic characteristics, operative data, survival data, and laboratory parameters were extracted. Neutrophil counts, lymphocyte counts, and albumin levels before surgery and 1 month postoperatively were analyzed. Results: In multivariable analysis adjusted for age, sex, and pathologic stage, high neutrophil count (hazard ratio [HR] 1.09, 95% confidence interval [CI] 1.01-1.17, p = 0.022) and low albumin (HR 0.45, 95% CI 0.27-0.74, p = 0.002) 1 month postoperatively were independent prognostic factors for overall survival. High neutrophil count (HR 1.09, 95% CI 1.02-1.16, p = 0.015) 1 month postoperatively was also an independent prognostic factor for recurrence-free survival after adjusting for age, sex, body mass index, extent of gastrectomy, and pathologic stage. Patients were classified into risk groups based on thresholds of 4.2 × 103 cells/mm3 and 4.1 g/dl for 1-month neutrophil count and albumin. High-risk groups had a significantly worse prognosis than low-risk groups for overall survival (HR 5.87, 95% CI 3.28-10.51, p <0.001) and recurrence-free survival (HR 1.52, 95% CI 1.07-2.16, p = 0.021). Conclusions: Neutrophil count and albumin level 1 month after curative surgery reflect long-term prognosis better than preoperative values. These parameters can be used to stratify patients with the same stage into different prognostic groups.ope

Chylous Ascites After Gastric Cancer Surgery: Risk Factors and Treatment Results

Purpose: Although chylous ascites is a frequent complication of radical gastrectomy for gastric cancer, proper diagnostic criteria and optimal treatment strategies have not been established. This study aimed to identify the clinical features of chylous ascites and evaluate the treatment outcomes. Materials and methods: We retrospectively analyzed the data of patients who underwent radical gastrectomy between 2013 and 2019. Diagnosis was made when milky fluid or elevated triglyceride levels (≥100 mg/dL) appeared in the drains without a preceding infection. The clinical features, risk factors, and treatment outcomes were assessed according to the initial treatment modalities for fasting and non-fasting groups. Results: Among the 7,388 patients who underwent radical gastrectomy for gastric cancer, 156 (2.1%) experienced chylous ascites. The median length of hospital stay was longer in patients with chylous ascites than in those without (median [interquartile range]: 8.0 [6.0-12.0] vs. 6.0 [5.0-8.0], P<0.001). Low body mass index (adjusted odds ratio [aOR]=0.9; P<0.001), advanced gastric cancer (aOR=1.51, P=0.024), open surgery (reference: laparoscopic surgery; aOR=1.87, P=0.003), and extent of surgical resection (reference: subtotal gastrectomy, total gastrectomy, aOR=1.5, P=0.029; proximal gastrectomy, aOR=2.93, P=0.002) were associated with the occurrence of chylous ascites. The fasting group (n=12) was hospitalized for a longer period than the non-fasting group (n=144) (15.0 [12.5-19.5] vs. 8.0 [6.0-10.0], P<0.001). There was no difference in grade III complication rate (16.7% vs. 4.2%, P=0.117) or readmission rate (16.7% vs. 11.1%, P=0.632) between the groups. Conclusions: A fat-controlled diet and medication without fasting provided adequate initial treatment for chylous ascites after radical gastrectomy for gastric cancer.ope